The interaction between virus and host defenses is complex. A defect in transformation-enhancing function of virus-infected human macrophages can account for the depression of lymphocyte transformation response to mitogens that is observed during in vitro influenza virus infection. Concurrently, the infected macrophages produce the antiviral substance interferon. Furthermore, fever or hyperthermia is a common response to infection with viruses, and has been associated with enhanced resistance to virus infection in animal models. The objective of this proposal is to further our understanding of the interaction between viruses and human immune defense mechanisms by determining whether the prior immunologic experience of the leukocyte donor modifies the effects of virus on transformation response and interferon production, whether the adverse effects of in vitro virus infection are related to the infectivity of the virus, whether certain of the effects are mediated by interferon, and whether hyperthermia, interferon, or ascorbic acid enhance macrophage resistance to or recovery from virus infection. Assays of function of human mononuclear leukocytes and highly purified macrophage and lymphocyte preparations (alone or re-combined) for transformation response to mitogen and interferon production are carried out with control cells and cells exposed to infectious and heat-inactivated virus, with an influenza virus strain familiar and unfamiliar to the leukocyte donors, with and without addition of interferon produced by virus-infected macrophages, with variation of temperature of incubation, and in the presence and absence of ascorbic acid. Assays for activation of control, interferon-treated and virus-infected macrophages are performed. Interferons produced are characterized. Respiratory syncytial virus and Sendai virus are also used to examine similarities or dissimilarities between respiratory viruses in interactions with human mononuclear leukocytes.